Staphylococcus aureus colonizes the anterior nares of nearly one-third of people and is the leading cause of skin and soft tissue infections in children and adults. Treatment of staphylococcal infections has become more challenging due to the emergence of community-associated methicillin-resistant S. aureus (CA-MRSA) organisms. In addition to the rise in infections due to CA-MRSA, asymptomatic nasal carriage with CA-MRSA also has increased. Specific groups appear to be at increased risk for CA-MRSA infections, such as adolescents, young adults, and sports team participants. As a result of the high morbidity and occasional mortality seen with CA-MRSA, we need to better understand what factors contribute to colonization and disease with this organism. Based on our preliminary data suggesting that infecting strains of CA-MRSA represent a subset of colonizing CA-MRSA strains, we hypothesize that CA-MRSA nasal colonization increases the risk for CA-MRSA infections, but only when the colonization strain expresses one or more virulence factors that promote the development of clinical disease. The overall goal of this proposal is to precisely define the epidemiology of S. aureus nasal carriage and subsequent risk for S. aureus infections. We have selected a population of college student-athletes, considered to be at higher risk for skin and soft tissue infections than the general population. Three integrated specific aims are proposed: 1) To prospectively determine the frequency of nasal carriage of S. aureus and CA-MRSA in a cohort of healthy sports team participants during the course of two seasons;2) to define the frequency of clinical staphylococcal infections with CA-MRSA and methicillin-susceptible S. aureus (MSSA) in the team members;and 3) to identify the microbial factors associated with nasal colonization and infection. This proposal is a natural extension of our earlier work studying nasal colonization with CA-MRSA in the pediatric population. It will be guided by an experienced mentorship team and will complement my training in pediatric infectious diseases, laboratory research, and epidemiology. Furthermore, the proposal supports my efforts to become an independent investigator defining the clinical and molecular epidemiology of staphylococcal carriage and disease.